Granted Patent B2

US 12,269,862 · App. 18/459,302 · Granted Apr 8, 2025

Inventors: Philip Stewart Low (West Lafayette, IN); Haiyan Chu (West Lafayette, IN); Yingjuan June Lu (West Lafayette, IN); Christopher Paul Leamon (West Lafayette, IN); Leroy W. Wheeler, II (West Lafayette, IN); Michael C. Jensen (Bainbridge Island, WA); James Matthaei (Seattle, WA)

Assignees: Endocyte, Inc.; Purdue Research Foundation; Seattle Children's Hospital

C07K14/7051A61K9/0019A61K9/0053A61K31/365A61K31/519A61K38/1774A61K39/4611A61P35/00C07K16/44C07K16/46C12N5/0636C12N5/0638A61K2239/38C07K2317/622

Abstract

Claims (19)

1. A method of treatment of a cancer in a human patient, wherein the human patient's bloodstream comprises a CAR T cell composition and one or more cancer cells, wherein the CAR T cell composition comprises CAR T cells that specifically bind to a targeting moiety and the one or more cancer cells specifically bind to a small molecule ligand;

the method comprising administering to a human patient a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises the small molecule ligand linked to the targeting moiety by a linker, wherein:

the small molecule ligand is folate and the targeting moiety is a fluorescein, fluorescein isothiocyanate (FITC), or NHS-fluorescein;

the compound, or the pharmaceutically acceptable salt thereof, is administered once weekly to the human patient, and wherein the compound, or the pharmaceutically acceptable salt thereof, is administered in a dose of about 10 nmoles/kg to about 50 nmoles/kg of body weight of the patient; and

the compound specifically binds to both the CAR T cells and to the one or more cancer cells, thereby treating the human patient for the cancer.

2. The method of claim 1 , wherein the CAR T cells comprise a CAR, wherein the CAR comprises an E2 anti-fluorescein antibody fragment.

3. The method of claim 2 , wherein the CAR comprises a FITC-E2 single chain variable region (scFv), an IgG4 hinge-CH2-CH3 spacer domain, a CD3% activation domain, and a 4-1BB co-stimulation domain.

4. The method of claim 2 , wherein the CAR comprises a polypeptide having at least about 80% identity to SEQ ID NO: 2 along a stretch of 200 nucleic acids.

5. The method of claim 1 , wherein the human patient has been administered, prior to administering the compound, a polynucleotide encoding a CAR directed to the targeting moiety.

6. The method of claim 1 , wherein the human patient has been administered, prior to administering the compound, a viral vector comprising a polynucleotide encoding a CAR directed to the targeting moiety.

7. The method of claim 1 , wherein the targeting moiety binds to an E2 anti-fluorescein antibody fragment.

8. The method of claim 7 , wherein the targeting moiety is fluorescein, or a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein the compound is

10. The method of claim 1 , wherein the compound is

11. The method of claim 1 , wherein the linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, poloxamer 407, or a combination thereof.

12. The method of claim 1 , wherein the cancer is a folate receptor expressing cancer.

13. The method of claim 1 , wherein cytokine release syndrome is not severe or is prevented in the human patient.

14. The method of claim 1 , wherein body weight loss in the human patient is less than about 20% during therapy.

15. The method of claim 1 , wherein the cancer comprises a tumor, wherein the tumor size is reduced, and wherein off-target toxicity does not occur or is reduced.

Assignments (8)

Continuity (8)

References Cited (400)

Cited By (1)

US 12,570,716